Brain interstitial fluid and intracellular distribution of phenytoin

After intravenous (i.v.) administration (10 mg/kg), the biodisposition of phenytoin (PHT) in serum (total and free concentration), cerebrospinal fluid (CSF), brain, and the interstitial fluid (IF) of the normal brain were determined in dogs. A sufficient volume of IF was obtained through a multiperforated polypropylene ball implanted into the left parietotemporal region for 4-5 weeks. PHT brain distribution coefficient values ranged between 1.9 and 3.75, while the ratios of IF to free serum PHT concentrations ranged between 0.19 and 1.04; thus, our data indicate that most of the free unbound PHT which enters the brain parenchyma accumulates in the cellular compartment. Furthermore, at 60 and 90 min the peak CSF and IF concentrations are delayed; thus, for PHT, an apparent diffusion front from the CSF into the extracellular space of the brain seems to occur.